Iron(III) Coordination Complexes as MRI Contrast Agents

纽约州立大学布法罗分校化学系的Janet R. Morrow教授正在开发新型的铁（Fe）配合物作为磁共振成像（MRI）造影剂，该项目由化学系化学结构、动态机制B和化学测量与成像项目资助。这项研究的目的是获得新的铁基试剂，在最新的MRI扫描仪中发现的场强下产生有效的MRI对比。铁是一种与生物相关的金属离子，可能是目前使用的钆的替代品，钆在成像中有耐受性问题。该项目位于有机化学和无机化学，以及生理学和成像物理学的界面，因此非常适合各级科学家的教育。莫罗教授在培养多样化的研究生和本科生方面有着良好的记录。涉及K-12学生和他们的科学老师的外展活动也是资助项目的一部分。大环铁（III）配合物正在开发作为MRI造影剂，目的是获得在临床上相关的3特斯拉(T)磁场下产生有效T1造影剂。配合物含有高度稳定的Fe（III）中心，不产生活性氧。将研究含有一个结合水或不含水配体的配合物，以评估外层和内层水对T1弛豫率的影响。第二个重点是开发顺磁性随温度和ph值变化的Fe（III）造影剂。这些自旋状态的变化将Fe（III）顺磁性CEST（化学交换饱和转移）剂和T1造影剂相互转换。EPR（电子顺磁共振）和穆斯堡尔光谱将用于表征配合物。为了研究弛豫度对磁场强度的依赖性，将在1.5 T， 3.0 T和4.7 T的MRI扫描仪上研究配合物，并获得选定的Fe（III）配合物的核磁共振色散谱。将研究最有效的Fe（III）造影剂，并将其与生物样品中的Gd（III）造影剂进行比较。

In this project funded by the Chemical Structure, Dynamic & Mechanism B and the Chemical Measurement & Imaging Programs of the Chemistry Division, Professor Janet R. Morrow of the Department of Chemistry at the University at Buffalo, State University of New York is developing new classes of iron (Fe) complexes as magnetic resonance imaging (MRI) contrast agents. The goal of this research is to obtain new iron-based agents that produce effective MRI contrast at the field strengths found in the newest MRI scanners. Iron is a biologically relevant metal ion that may be an alternative to the currently used gadolinium, which has tolerance issues in imaging. The project lies at the interface of organic and inorganic chemistry, as well as physiology and imaging physics and is therefore well suited to the education of scientists at all levels. Professor Morrow has a strong record of educating a diverse group of graduate and undergraduate students. Outreach activities involving K-12 students and their science teacher are also be part of the funded project. Macrocyclic Fe(III) complexes are being developed as MRI contrast agents with the goal of obtaining agents that produce effective T1 contrast at the clinically relevant magnetic field of 3 Tesla (T). The complexes contain highly stabilized Fe(III) centers that do not produce reactive oxygen species. Complexes that contain one bound water or no water ligands are to be studied to assess the effect of outer versus innersphere water on T1 relaxivity. A second emphasis is to develop Fe(III) contrast agents that change paramagnetic properties with temperature and pH. These spin state changes interconvert Fe(III) paramagnetic CEST (Chemical Exchange Saturation Transfer) agents and T1 contrast agents. EPR (Electron paramagnetic resonance) and Mossbauer spectroscopy will be used for characterization of the complexes. To study the magnetic field strength dependence of relaxivity, the complexes will be studied on MRI scanners at 1.5 T, 3.0 T and 4.7 T. A nuclear magnetic resonance dispersion spectrum will be obtained for selected Fe(III) complexes. The most effective Fe(III) contrast agents will be studied and compared to Gd(III) contrast agents in biological samples.